Nine decades of antibiotics: a story with two endings…

I did a talk today in Portugal covering the nine decades since Fleming discovered the effects of Penicillium sp. in 1928. I thought it would be interesting to have two endings to the talk: an upbeat one, and a doomsday one.

You can download the slides from the talk here. I decided to use MRSA and CPE as two examples to illustrate the wax, wane, and drivers of AMR. The differences in MRSA and CPE prevalence across Europe tell us a lot, I think, about what works to keep AMR under control. Principally: optimal use of antibiotics driven by an antimicrobial stewardship programme, a focus on infection prevention and control, and well-funded healthcare systems and infrastructure.

The endings reflecting on what could happen over the next 10 years were based on the following factors, pulled together from various sources (Figure 1). And by way of disclaimer, creative writing never was my strong point…

Figure 1: Key determinants for preventing AMR.

The upbeat ending

The year is 2028 and I’m delighted to report that we have made significant progress in tackling AMR.

We have succeeded in selling the message to our non-expert healthcare colleagues that we can’t rely on antibiotic for ever, and prevention is better than cure.

Real progress has been made in reducing antibiotic consumption. The global ban on non-therapeutic use of antibiotics in animal husbandry has been pivotal, and we have reduced the use of key antibiotics in human medicine in hospitals and the community too.

The introduction of that shiny new point-of-care diagnostic system that gives you an instant identification of causal pathogen, species, and antibiotic resistance profile sure has been helpful [I did say this was creative].

WHO’s GLASS surveillance system has really taken off – pretty much every country on the globe now contributes a rich dataset. And the WHO-funded expert taskforce visiting countries that are struggling has made a difference.

The introduction of effective phage therapy to complement antibiotics has worked well. It has helped us to reduce the use of antibiotics, and reserve the newer ones for when we need them most.

Whilst the Review on AMR in 2016 was a good start in highlighting the financial burden of HCAI, it wasn’t until this became a key political contention in the US Presidential Election Race in 2020 that the world finally took stock of the spiralling cost of AMR.

There have been no genuinely new antibiotics, but a new model of discovery and development has mobilised the pharmaceutical industry, and we have a stream of improved antibiotics now hitting the market.

The global public health awareness campaign of 2023 has left a sustained legacy. We don’t talk about “AMR” anymore – it’s far too technical and the public don’t understand. Instead, we talk in terms of [answers on a postcard].

Finally, senior roles in AMR clinical practice and research are some of the most sought-after and best-paid in medicine. In fact, several leading orthopaedic surgeons have decided to retrain as clinical microbiologists.

The impact of all of this has been impressive, as you can see from the latest data from EARS-Net (Figure 2). Invasive infections caused by carbapenem-resistant Klebsiella pneumoniae are now trending down across Europe and elsewhere in the world, and we see the same trends with MRSA, VRE, C. difficile and others! You might even say that we’ve turned a corner, and the future of AMR is hopeful.

The year is 2028 and I’m sad to report that we have made little progress in tackling AMR.

We have failed in selling the message to our non-expert healthcare colleagues that we can’t rely on antibiotic for ever, and prevention is better than cure. We still talk passionately about this to whoever will listen.

Antibiotic consumption is rising inexorably. We have achieved no control on the non-therapeutic use of antibiotics in animal husbandry. And antibiotic use, especially of the carbapenems, is now rife in both hospitals and the community.

Despite numerous prize funds and political rhetoric, no effective point-of-care diagnostic system has materialised. Most samples continue to be sent to the lab and most antibiotic prescribing continues to be empiric.

WHO’s GLASS surveillance system failed. The project was shelved in 2022. Whilst low and middle income countries tried to participate, high-income countries didn’t seem interested, for some reason.

Phage therapy didn’t come off. Despite a lot of research and well-designed trials, bacteria are just too nimble to be pinned down by even advanced, engineered phage cocktails. After all, they have been around together for a very long time!

We still like to talk about the cost and impact of AMR on our healthcare systems, but it seems that our colleagues have bigger fish to fry.

There have been no genuinely new antibiotics, and no new model for pharmaceutical discovery and development. Although the latter is still planned.

There are some very clever and expensive local, regional, and even national awareness campaigns around AMR. But it’s amazing how quickly the public move on to the next thing!

Finally, senior roles in AMR clinical practice and research remain some of the lowest paid medicine. In fact, several leading clinical microbiologists have decided to retrain as orthopaedic surgeons.

The impact of all of this has been dramatic, as you can see from the latest data from EARS-Net (Figure 4). Invasive infections caused by carbapenem-resistant Klebsiella pneumoniae are now rife and trending up across Europe and elsewhere in the world, and we see the same trends with MRSA, VRE, C. difficile and others. The future of AMR is bleak.

Back now to 2018. I took a quick poll on this site and on Twitter to get a sense of how people are feeling about the next decade in AMR (Figure 4).

Figure 4: How do you feel about the future of AMR?

Thanks to all who participated. As you can see, most people feel either negative or neutral, and a definite minority feel positive. Whilst I can understand this, believe it or not, I am one of the few who voted positively. I know we face an uphill struggle, and the odds are stacked against us. But remarkable progress has been made in reducing MRSA bloodstream infections in some parts of the world. And we are beginning to see antibiotic consumption reducing in the UK. So, let’s choose the upbeat ending to this AMR story, shall we?